1. Field of the Invention
This invention lies in the field of chromatography, and particularly the chromatographic technique known in the art as simulated moving bed chromatography (SMB).
2. Description of the Prior Art
Many solid chemical species that are synthesized in liquid reaction media must be recovered and various impurities must be removed after the reaction has been terminated. The impurities may include degradation products, unreacted starting materials, and the products of competing reactions. Product recovery is performed by crystallization, which serves two purposes: the first is to recover the product as a solid, and often a solid of a particular crystal structure (such as a polymorph), and the second is to purify the product by crystallizing the product preferentially over the impurities. To avoid or minimize the precipitation of impurities, crystallization is commonly performed in such a way that a certain amount of product remains in solution. This uncrystallized product is thus lost to the filtrate which is then discarded as a waste effluent of the process. Complete crystallization of the product can result in precipitation of the impurities with the product, requiring additional purification stages to achieve the desired purity. This downstream purification typically includes filtration, precipitation, centrifugation, or other means of compacting the product into a filter cake, followed by washing the filter cake with a wash liquid, which is typically the solvent used in the reaction medium. In many cases, several washes are required to remove the filtrate and associated impurities from the filter cake. During each wash, a small amount of crystallized product is redissolved and lost in the wash. For all of these reasons, significant losses of product are common, and obtaining a product of high purity often entails a sacrifice in yield. A loss of 10% to 30% of the product to the filtrate or to the combined filtrate and wash liquid is not unusual.
With significant amounts of high-value product in the filtrate, processes for recovery of high-purity product from the filtrate with an impurity profile similar to that of the first intent material are of great interest, particularly in the pharmaceutical industry. In certain cases, the filtrate itself can be subjected to crystallization and a “second crop” can be isolated to increase the overall yield. In most cases, however, this second crystallization fails to meet the purity criteria because the level of impurities is higher in the filtrate than in the initial product mixture, and these impurities either prevent the second crop crystallization from occurring or make the second crop crystallization uneconomical because of the low yield.